This invention relates to novel 4" and 11-modified macrolides that are useful as antibacterial agents and antiprotozoa agents and other applications (e.g., anticancer, atherosclerosis, gastric motility reduction, etc.) in mammals, including man, as well as in fish and birds. This invention also relates to pharmaceutical compositions containing the novel compounds and to methods of treating bacterial infections and protozoa infections and in mammals, fish and birds by administering the novel compounds to mammals, fish and birds requiring such treatment.
Macrolide antibiotics are known to be useful in the treatment of a broad spectrum of bacterial infections and protozoa infections in mammals, fish and birds. Such antibiotics include various derivatives of erythromycin A such as azithromycin which is commercially available and is referred to in U.S. Pat. Nos. 4,474,768 and 4,517,359, both of which are incorporated herein by reference in their entirety. Additional macrolides are referred to in U.S. patent application Ser. No. 60/063,676, filed Oct. 29, 1997 (Yong-Jin Wu), U.S. application Ser. No. 60/063,161, filed Oct. 29, 1997 (Yong-Jin Wu), U.S. application Ser. No. 60/054,866, filed Aug. 6, 1997(Hiroko Masamune, Yong-Jin Wu, Takushi Kaneko and Paul R. McGuirk), U.S. application Ser. No. 60/049,980, filed Jun. 11, 1997 (Brian S. Bronk, Henry Cheng, E. A. Glaser, Michael A. Letavic, Takushi Kaneko and Bingwei V. Yang), U.S. application Ser. No. 60/049,348, filed Jun. 11, 1997 (Brian S. Bronk, Henry Cheng, E. A. Glaser, Michael A. Letavic, Takushi Kaneko and Bingwei V. Yang), International Application No. PCT/GB97/01810 filed Jul. 4, 1997 (Peter Francis Leadlay, James Staunton, Jesus Cortes and Michael Stephen Pacey), International Application No. PCT/GB97/01819 filed Jul. 4, 1997 (Peter Francis Leadlay, James Staunton, and Jesus Cortes), U.S. application Ser. No. 60/070,343, filed Jan. 2, 1998 (Dirlam), U.S. application Ser. No. 60/070,358, filed Jan. 2, 1998 (Yong-Jin Wu) and U.S. application Ser. No. 60/097,075, filed Aug. 19, 1998 (Hengmiao Cheng, Michael A. Letavic, Carl B. Ziegler, Jason K. Dutra, Peter Bertinato, Brian S. Bronk), all of which are incorporated herein by reference in their entirety. Like azithromycin and other macrolide antibiotics, the novel macrolide compounds of the present invention possess potent activity against various bacterial infections and protozoa infections as described below.